Automatic versus manual pressure support reduction in the weaning of post-operative patients: a randomised controlled trial

Introduction Reduction of automatic pressure support based on a target respiratory frequency or mandatory rate ventilation (MRV) is available in the Taema-Horus ventilator for the weaning process in the intensive care unit (ICU) setting. We hypothesised that MRV is as effective as manual weaning in post-operative ICU patients. Methods There were 106 patients selected in the postoperative period in a prospective, randomised, controlled protocol. When the patients arrived at the ICU after surgery, they were randomly assigned to either: traditional weaning, consisting of the manual reduction of pressure support every 30 minutes, keeping the respiratory rate/tidal volume (RR/TV) below 80 L until 5 to 7 cmH(2)O of pressure support ventilation (PSV); or automatic weaning, referring to MRV set with a respiratory frequency target of 15 breaths per minute (the ventilator automatically decreased the PSV level by 1 cmH(2)O every four respiratory cycles, if the patient`s RR was less than 15 per minute). The primary endpoint of the study was the duration of the weaning process. Secondary endpoints were levels of pressure support, RR, TV (mL), RR/TV, positive end expiratory pressure levels, FiO(2) and SpO(2) required during the weaning process, the need for reintubation and the need for non-invasive ventilation in the 48 hours after extubation. Results In the intention to treat analysis there were no statistically significant differences between the 53 patients selected for each group regarding gender (p = 0.541), age (p = 0.585) and type of surgery (p = 0.172). Nineteen patients presented complications during the trial (4 in the PSV manual group and 15 in the MRV automatic group, p < 0.05). Nine patients in the automatic group did not adapt to the MRV mode. The mean +/- sd (standard deviation) duration of the weaning process was 221 +/- 192 for the manual group, and 271 +/- 369 minutes for the automatic group (p = 0.375). PSV levels were significantly higher in MRV compared with that of the PSV manual reduction (p < 0.05). Reintubation was not required in either group. Non-invasive ventilation was necessary for two patients, in the manual group after cardiac surgery (p = 0.51). Conclusions The duration of the automatic reduction of pressure support was similar to the manual one in the postoperative period in the ICU, but presented more complications, especially no adaptation to the MRV algorithm. Trial Registration Trial registration number: ISRCTN37456640

Low-dose estrogen therapy does not change postexercise hypotension, sympathetic nerve activity reduction, and vasodilation in healthy postmenopausal women

The aim of this study was to determine whether estrogen therapy enhances postexercise muscle sympathetic nerve activity (MSNA) decrease and vasodilation, resulting in a greater postexercise hypotension. Eighteen postmenopausal women received oral estrogen therapy (ET; n = 9, 1 mg/day) or placebo (n = 9) for 6 mo. They then participated in one 45-min exercise session (cycle ergometer at 50% of oxygen uptake peak) and one 45-min control session (seated rest) in random order. Blood pressure (BP, oscillometry), heart rate (HR), MSNA (microneurography), forearm blood flow (FBF, plethysmography), and forearm vascular resistance (FVR) were measured 60 min later. FVR was calculated. Data were analyzed using a two-way ANOVA. Although postexercise physiological responses were unaltered, HR was significantly lower in the ET group than in the placebo group (59 +/- 2 vs. 71 +/- 2 beats/min, P < 0.01). In both groups, exercise produced significant decreases in systolic BP (145 +/- 3 vs. 154 +/- 3 mmHg, P = 0.01), diastolic BP (71 +/- 3 vs. 75 +/- 2 mmHg, P = 0.04), mean BP (89 +/- 2 vs. 93 +/- 2 mmHg, P = 0.02), MSNA (29 +/- 2 vs. 35 +/- 1 bursts/min, P < 0.01), and FVR (33 +/- 4 vs. 55 +/- 10 units, P = 0.01), whereas it increased FBF (2.7 +/- 0.4 vs. 1.6 +/- 0.2 ml (.) min(-1) (.) 100 ml(-1), P = 0.02) and did not change HR (64 +/- 2 vs. 65 +/- 2 beats/min, P = 0.3). Although ET did not change postexercise BP, HR, MSNA, FBF, or FVR responses, it reduced absolute HR values at baseline and after exercise.

New SMS mutation leads to a striking reduction in spermine synthase protein function and a severe form of Snyder-Robinson X-linked recessive mental retardation syndrome

We report the identification of a novel mutation at a highly conserved residue within the N-terminal region of spermine synthase (SMS) in a second family with Snyder-Robinson X-linked mental retardation syndrome ( OMIM 309583). This missense mutation, p.G56S, greatly reduces SMS activity and leads to severe epilepsy and cognitive impairment. Our findings contribute to a better delineation and expansion of the clinical spectrum of Snyder-Robinson syndrome, support the important role of the N-terminus in the function of the SMS protein, and provide further evidence for the importance of SMS activity in the development of intellectual processing and other aspects of human development.

Programmed hypertension in rats treated with a NF-kappa B inhibitor during nephrogenesis: renal mechanisms

Suppression of the renin-angiotensin system (RAS) during murine lactation causes progressive renal injury, indicating a physiological action of angiotensin II on nephrogenesis. The nuclear factor NF-kappa B system is one of the main intracellular mediators of angiotensin II. We investigated whether inhibition of this system with pyrrolidine dithiocarbamate (PDTC) during rat nephrogenesis would lead to similar hypertension and renal injury as observed with RAS suppressors. Immediately after delivery, 32 Munich-Wistar dams, each nursing 6 male pups, were divided into 2 groups: C, untreated, and PDTC, receiving PDTC, 280 mg kg(-1) day(-1) orally, during 21 days. After weaning, the offspring were followed until 10 months of age without treatment. Adult rats that received neonatal PDTC exhibited stable hypertension and myocardial injury, without albuminuria. To gain additional insight into this process, the renal expression of RAS components and sodium transporters were determined by quantitative real-time PCR (qRT-PCR) at 3 and 10 months of life. Renal renin and angiotensinogen were upregulated at 3 and downregulated at 10 months of age, suggesting a role for early local RAS activation. Likewise, there was early upregulation of the proximal sodium/glucose and sodium/bicarbonate transporters, which abated later in life, suggesting that additional factors sustained hypertension in the long run. The conclusions drawn from the findings were as follows: (1) an intact NF-jB system during nephrogenesis may be essential to normal renal and cardiovascular function in adult life; (2) neonatal PDTC represents a new model of hypertension, lacking overt structural injury or functional impairment of the kidneys; and (3) hypertension in this model seems associated with early temporary activation of renal RAS and sodium transporters. Hypertension Research (2011) 34, 693-700; doi: 10.1038/hr. 2011.4; published online 17 February 2011

The synergy between structural stability and DNA-binding controls the antibody production in EPC/DOTAP/DOPE liposomes and DOTAP/DOPE lipoplexes

We present a comparative study of the physico-chemical properties, in vitro cytotoxicity and in vivo antibody production of surface-complexed DNA in EPC/DOTAP/DOPE (50/25/25% molar) liposomes and DOTAP/DOPE (50/50% molar) lipoplexes. The study aims to correlate the biological behavior and structural properties of the lipid carriers. We used DNA-hsp65, whose naked action as a gene vaccine against tuberculosis has already been demonstrated. Additionally, surface-complexed DNA-hsp65 in EPC/DOTAP/DOPE (50/25/25% molar) liposomes was effective as a single-dose tuberculosis vaccine. The results obtained showed that the EPC inclusion stabilized the DOTAP/DOPE structure, producing higher melting temperature and lower zeta potential despite a close mean hydrodynamic diameter. Resemblances in morphologies were identified in both structures, although a higher fraction of loaded DNA was not electrostatically bound in EPC/DOTAP/DOPE. EPC also induced a striking reduction in cytotoxicity, similar to naked DNA-hsp65. The proper immune response lead to a polarized antibody production of the IgG2a isotype, even for the cytotoxic DOTAP/DOPE. However, the antibody production was detected at 15 and 30 days for DOTAP/DOPE and EPC/DOTAP/DOPE, respectively. Therefore, the in vivo antibody production neither correlates with the in vitro cytotoxicity, nor with the structural stability alone. The synergistic effect of the structural stability and DNA electrostatic binding upon the surface of structures account for the immunological effects. By adjusting the composition to generate proper packing and cationic lipid/DNA interaction, we allow for the optimization of liposome formulations for required immunization or gene therapy. In a specific manner, our results contribute to studies on the tuberculosis therapy and vaccination. (C) 2009 Elsevier B.V. All rights reserved.

EFFECT OF THE TEMPERATURE AND pH ON METHANOL RELEASE IN COFFEE BREW SWEETENED WITH ASPARTAME

Methanol is an alcohol which is metabolized to folmaldehyde in humans. It is a very toxic substance, responsible for blindness in cases of methanol intoxication. This study shows the production of methanol when aspartame is used to sweeten coffee brew. The temperature versus pH binomium was also tested. When assayed at 90 degrees C coffee brew+aspartame and aspartame solution showed an increase in methanol release of 17.8 and 19.3%, respectively, as compared with coffee brew. At 180 degrees C, the increase was 32.5 and 26.3%, respectively. Our data revealed a protective effect of the pH of coffee on the degradation of aspartame and formation of methanol; an important fact, mainly for specific populations that use aspartame, like diabetics.

Neuromuscular activity of BaTX, a presynaptic basic PLA(2) isolated from Bothrops alternatus snake venom

We have previously isolated a Lys49 phospholipase A(2) homolog (BaTX) from Bothrops alternatus snake venom using a combination of molecular exclusion chromatography and reverse phase HPLC and shown its ability to cause neuromuscular blockade. In this work, we describe a one-step procedure for the purification of this toxin and provide further details of its neuromuscular activity. The toxin was purified by reverse phase HPLC and its purity and molecular mass were confirmed by SIDS-PAGE, MALDI-TOF mass spectrometry, amino acid analysis and N-terminal sequencing. BaTX (0.007-1.4 mu M) produced time-dependent, irreversible neuromuscular blockade in isolated mouse phrenic nerve-diaphragm and chick biventer cervicis preparations (time to 50% blockade with 0.35 mu M toxin: 58 +/- 4 and 24 +/- 1 min, respectively; n = 3-8; mean +/- S.E.) without significantly affecting the response to direct muscle stimulation. In chick preparations, contractures to exogenous acetylcholine (55 and 110 mu M) or KCl (13.4 mM) were unaltered after complete blockade by all toxin concentrations. These results, which strongly suggested a presynaptic mechanism of action for this toxin, were reinforced by (1) the inability of BaTX to interfere with the carbachol-induced depolarization of the resting membrane, (2) a significant decrease in the frequency and amplitude of miniature end-plate potentials, and (3) a significant reduction (59 +/- 4%, n=12) in the quantal content of the end-plate potentials after a 60 min incubation with the toxin (1.4 mu M). In addition, a decrease in the organ bath temperature from 37 degrees C to 24 degrees C and/or the replacement of calcium with strontium prevented the neuromuscular blockade, indicating a temperature-dependent effect possibly mediated by enzymatic activity. (C) 2009 Elsevier Inc. All rights reserved.

Reduction of ICAM-1 expression by carbon monoxide via soluble guanylate cyclase activation accounts for modulation of neutrophil migration

Previously, it was demonstrated that the heme/heme oxygenase (HO)/carbon monoxide (CO) pathway inhibits neutrophil recruitment during the inflammatory response. Herein, we addressed whether the inhibitory effect of the HO pathway on neutrophil adhesion and migration involves the reduction of intracellular adhesion molecule type (ICAM)-1 and beta(2)-integrin expression. Mice pretreated with a specific inhibitor of inducible HO (HO-1), zinc protoporphyrin (ZnPP) IX, exhibit enhanced neutrophil adhesion and migration induced by intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS). These findings are associated with an increase in ICAM-1 expression on mesentery venular endothelium. In accordance, HO-1 inhibition did not enhance LPS-induced neutrophil migration and adhesion in ICAM-1-deficient mice. Furthermore, the treatment with a CO donor (dimanganese decacarbonyl, DMDC) that inhibits adhesion and migration of the neutrophils, reduced LPS-induced ICAM-1 expression. Moreover, neither DMDC nor ZnPP IX treatments changed LPS-induced beta(2)-integrin expression on neutrophils. The effect of CO on ICAM-1 expression seems to be dependent on soluble guanylate cyclase (sGC) activation, since 1H-(1,2,4)oxadiazolo (4,3-a)quinoxalin-1-one (sGC inhibitor) prevented the observed CO effects. Finally, it was observed that the nitric oxide (NO) anti-inflammatory effects on ICAM-1 expression appear to be indirectly mediated by HO-1 activation, since the inhibition of HO-1 prevented the inhibitory effect of the NO donor (S-nitroso-N-acetylpenicillamine) on LPS-induced ICAM-1 expression. Taken together, these results suggest that CO inhibits ICAM-1 expression on endothelium by a mechanism dependent on sGC activation. Thus, our findings identify the HO-1/CO/guanosine 3`5`-cyclic monophosphate pathway as a potential target for the development of novel pharmacotherapy to control neutrophil migration in inflammatory diseases.

Determination of temperature variation during the individual steps of the production of hospital diets of modified consistency

Background & aim: Many disease outbreaks of food origin are caused by foods prepared in Food Service and Nutrition Units of hospitals, affecting hospitalized patients who, in most cases, are immunocompromised and therefore at a higher risk of severe worsening of their clinical status. The aim of this study was to determine the variations in temperature and the time-temperature factor of hospital diets. Methods: The time and temperature for the preparation of 4 diets of modified consistency were determined on 5 nonconsecutive days in a hospital Diet and Nutrition Unit at the end of preparation and during the maintenance period, portioning and distribution at 3 sites, i.e., the first, the middle and the last to receive the diets. Results and discussion: All foods reached an adequate temperature at the end of cooking, but temperature varied significantly from the maintenance period to the final distribution, characterizing critical periods for microorganism proliferation. During holding, temperatures that presented a risk were reached by 16.7% of the meats and 59% of the salads of the general diet, by 16.7% of the garnishes in the bland diet and by 20% of the meats and garnishes in the viscous diet. The same occurred at the end of distribution for 100% of the hot samples and of the salads and for 61% of the desserts. None of the preparations remained at risk temperature for a time exceeding that established by law. Conclusion: The exposure to inadequate temperature did not last long enough to pose risks to the patient.

Effects of intrapulpal temperature change induced by visible light units on the metabolism of odontoblast-like cells

Purpose: To investigate the effects of intrapulpal temperature changes induced by a quartz tungsten halogen (QTH) and a light emitting diode (LED) curing units on the metabolism of odontoblast-like cells. Methods: Thirty-six 0.5 mm-thick dentin discs obtained from sound human teeth were randomly assigned into three groups: QTH, LED and no light (control). After placement of the dentin discs in pulp chamber devices, a thermistor was attached to the pulpal surface of each disc and the light sources were applied on the occlusal surface. After registering the temperature change, odontoblast-like cells MDPC-23 were seeded on the pulpal side of the discs and the curing lights were again applied. Cell metabolism was evaluated by the MTT assay and cell morphology was assessed by SEM. Results: In groups QTH and LED the intrapulpal temperature increased by 6.4 degrees C and 3.4 degrees C, respectively. The difference between both groups was statistically significant (Mann-Whitney; P< 0.05). QTH and LED reduced the cell metabolism by 36.4% and 33.4%, respectively. Regarding the cell metabolism, no statistically significant difference was observed between both groups (Mann-Whitney; P> 0.05). However, when compared to the control, only QTH significantly reduced the cell metabolism (Mann-Whitney; P< 0.05). It was concluded that the irradiance of 0.5 mm-thick human dentin discs with a QTH in comparison to a LED curing unit promoted a higher temperature rise, which propagates through the dentin negatively affecting the metabolism of the underlying cultured pulp cells. (Am J Dent 2009;22:151-156).

Temperature safety profile of laparoscopic devices: Harmonic ACE (ACE), Ligasure V (LV), and plasma trisector (PT)

Background Reports of iatrogenic thermal injuries during laparoscopic surgery using new generation vessel-sealing devices, as well as anecdotal reports of hand burn injuries during hand-assisted surgeries, have evoked questions about the temperature safety profile and the cooling properties of these instruments. Methods This study involved video recording of temperatures generated by different instruments (Harmonic ACE [ACE], Ligasure V [LV], and plasma trisector [PT]) applied according the manufacturers` pre-set settings (ACE setting 3; LV 3 bars, and the PT TR2 50W). The video camera used was the infrared Flex Cam Pro directed to three different types of swine tissue: (1) peritoneum (P), (2) mesenteric vessels (MV), and (3) liver (L). Activation and cooling temperature and time were measured for each instrument. Results The ACE device produced the highest temperatures (195.9 degrees +/- 14.5 degrees C) when applied against the peritoneum, and they were significantly higher than the other instruments (LV = 96.4 degrees +/- 4.1 degrees C, and PT = 87 degrees +/- 2.2 degrees C). The LV and PT consistently yielded temperatures that were < 100 degrees C independent of type of tissue or ""on""/ ""off"" mode. Conversely, the ACE reached temperatures higher than 200 degrees C, with a surprising surge after the instrument was deactivated. Moreover, temperatures were lower when the ACE was applied against thicker tissue (liver). The LV and PT cooling times were virtually equivalent, but the ACE required almost twice as long to cool. Conclusions The ACE increased the peak temperature after deactivation when applied against thick tissue (liver), and the other instruments inconsistently increased peak temperatures after they were turned off, requiring few seconds to cool down. Moreover, the ACE generated very high temperatures (234.5 degrees C) that could harm adjacent tissue or the surgeon`s hand on contact immediately after deactivation. With judicious use, burn injury from these instruments can be prevented during laparoscopic procedures. Because of the high temperatures generated by the ACE device, particular care should be taken when it is used during laparoscopy.